Particulate carriers are commonly used in the pharmaceutical arts. For example, particulate carriers have been used with adsorbed or entrapped antigens in attempts to elicit adequate immune responses. Such carriers present multiple copies of a selected antigen to the immune system and are believed to promote trapping and retention of antigens in local lymph nodes. The particles can be phagocytosed by macrophages and can enhance antigen presentation through cytokine release.
For example, commonly owned International Publication No. WO 98/33487 and co-pending Pub. No. US 2003/0049298 describe the use of antigen-adsorbed and antigen-encapsulated microparticles to stimulate immunological responses, including cell-mediated immunological responses, as well as methods of making the microparticles. Polymers used to form the microparticles include poly(lactide) and poly(lactide-co-glycolide)(PLG).
Commonly owned International Publication No. WO 00/06123 and WO 01/36599 and U.S. Pat. No. 6,884,435 disclose methods of making microparticles having adsorbed macromolecules, including polynucleotides and polypeptide antigens. The microparticles comprise, for example, a biodegradable polymer and are formed using, for example, cationic, anionic or nonionic detergents. Microparticles containing anionic detergents can be used with positively charged macromolecules, such as polypeptides. Microparticles containing cationic detergents can be used with negatively charged macromolecules, such as DNA. The use of such microparticles to stimulate immunological responses, including cell-mediated immunological responses, is also disclosed.
Commonly owned International Patent Appln. No. PCT/US06/46212 describes sterile-filtered lyophilized nanoparticle compositions which contain at least one biodegradable polymer, at least one surfactant, at least one cryoprotective agent, and at least one antigen. Also disclosed are methods of making and using such compositions and kits supplying such compositions. Nanoparticles are created using the nanoprecipitation method.